The matching of an extended set of significant antigens (ExtendedMatch™) will minimize adverse transfusion reactions (see Hillyer et al., Blood Banking and Transfusion Medicine; published. by Churchill Livingston, Philadelphia Pa.) and other potential complications arising from allo-immunization. This is so particularly for patients receiving multiple transfusions who, as in the case of hemoglobinopathies, may otherwise become refractory to transfusion. However, the virtually exclusive current practice of invoking serological methods to determine antigen phenotypes, one at a time, creates considerable logistical and economic challenges for the effective implementation of this standard. Thus, the use of serological typing methods to identify large numbers of prospective donors with a desirable repertoire of major and minor transfusion antigens so as to support diverse inventories of blood products will require a substantial investment of both time and resources, especially given the increasing expense for increasingly rare serological reagents. Further, in part reflecting this investment, the cost of acquiring such units, typically priced to include a surcharge per desirable antigenic marker matched per unit, can be prohibitive. The procurement of matched blood for recipients, who either display an uncommon antigen or lack a common antigen, is particularly problematic. While collections of transfusion donors with rare minor blood group phenotypes have been initiated (see the Redcross website), they remain limited, for example with currently only 30,000 donors registered in the American Rare Donor program.
Recent technological innovation (Hashmi et al., Transfusion, 45, 680-688 (2005)) has the potential to enable the replacement of serological methods of transfusion antigen determination by methods of genetic analysis. These methods would not only obviate the need for rare and expensive serological reagents but also would permit the concurrent (“multiplex”) analysis of an entire set of genetic determinants of transfusion antigen phenotypes. Large-scale multiplexed transfusion antigen genotyping, particularly when combined with non-invasive collection of samples such as “finger sticks” or buccal swabs, would provide a basis for rapidly surveying donors for an extended set of clinically significant antigens and to construct a diversified inventory prior to collecting, processing and storing blood products.
The concept of a candidate donor inventory previously has been implemented in the form of bone marrow donor registries which have been organized around the world to provide a diverse pool of candidate donors who can be genetically matched to patients by comparing the relevant genetic loci within the Human Leukocyte Antigen (HLA) complex. However, in view of the highly variable nature of the HLA gene complex, these registries, in order to ensure a finite probability that a request for a specific HLA type can be filled, must acquire and maintain a large inventory by “taking all comers” Yet, by the same token of genetic diversity within the HLA complex, the likelihood of any donor being called upon is small, repeat donation exceedingly rare, and inventory turnover low. In view of the substantial expense of recruiting and typing prospective bone marrow donors, the operation of such repositories in an economically viable manner is difficult at best, and in fact, generally requires public expenditure (as in the case of the National Marrow Donor Program, see their website) or private philanthropy (as in the case of private registries maintained by foundations around the world).
In contrast to bone marrow and organ donation, blood donation is relatively painless, and is performed in high volume, at an annual rate of approximately 50 million donations worldwide, routinely including repeat donation, creating high turnover in existing supplies of blood products. The introduction of large-scale genetic typing into transfusion diagnostics would permit a systematic increase in the diversity of the inventory to support an ExtendedMatch strategy in a practical and cost-effective manner. A diversified inventory in turn would permit the rapid selection of a donor for a recipient with known transfusion antigen genotype (TAG) by genetic cross matching (see U.S. application Ser. No. 11/298,763, incorporated by reference).
The selection of compatible candidate blood donors in response to requests posted to a registry of such donors would facilitate the timely procurement of compatible blood products. This would be desirable in order to improve the public health and to minimize the cost accruing in the health care system in the form of unnecessarily prolonged hospital stays and adverse clinical effects arising from the administration of incorrectly or incompletely matched units of blood products such as red cell or platelets.
The operation of a transfusion donor registry of diverse composition and “critical mass” in a commercially viable manner calls for an effective organizational architecture and for strategies of optimal inventory management that represent a departure from the passive repository concept.